This proposal represents a continuation of the past 27 years of research into the mechanisms of ventilation perfusion ratio distribution in the lungs. In the past years, we have addressed the mechanisms affecting VA/Q heterogeneity using the multiple inert gas elimination technique (MIGET), a tool for quantitatively assessing pulmonary gas exchange. MIGET yields global information about VA/Q distribution without providing specific information regarding either Q or VA distributions. The proposed research will take advantage of our past work coupled with the recent development of the use of fluorescent microspheres to assess regional distribution of perfusion to small 1.9 cm3 volumes of the lung and the phase IIi slope ratio analysis of N2 washout to assess mechanisms of ventilation distribution. These methods allow resolution of blood flow within small regions of the lung and separation of ventilation inhomogeneity into its central (airway) and peripheral (acinar) components. We use these methods to separate the relative importance of several factors (lung blood flow, lung blood flow, lung volume, alveolar PO2, alveolar PCO2, gravity and exercise) in determining VA/Q heterogeneity. Most of our experiments will focus on the dog (with a reduced hypoxic pulmonary vasoconstriction (HPV) and increased collateral ventilation) and the pig (increased Hpv and no collateral ventilation). These animals will be studied at different levels of resolution; the whole animal, the separated lung preparation and the isolated lobule preparation. In order to study unanesthetized animals, the thoroughbred horse will be studied as a model for evaluating high cardiac output states and large vertical lung size. We will also use the centrifuged (high-gravity) unanesthetized pig model to evaluate the role of gravity and positive pressure breathing on lung function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL012174-30
Application #
2609184
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1977-04-01
Project End
1999-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
30
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Chang, Hung; Lai-Fook, Stephen J; Domino, Karen B et al. (2006) Redistribution of blood flow and lung volume between lungs in lateral decubitus postures during unilateral atelectasis and PEEP. Chin J Physiol 49:83-95
Chang, Hung; Lai-Fook, Stephen J; Domino, Karen B et al. (2006) Ventilation and perfusion distribution during altered PEEP in the left lung in the left lateral decubitus posture with unchanged tidal volume in dogs. Chin J Physiol 49:74-82
Robertson, H Thomas; Kreck, Thomas C; Krueger, Melissa A (2005) The spatial and temporal heterogeneity of regional ventilation: comparison of measurements by two high-resolution methods. Respir Physiol Neurobiol 148:85-95
Hubler, Matthias; Souders, Jennifer E; Shade, Erin D et al. (2002) Effects of perfluorohexane vapor on relative blood flow distribution in an animal model of surfactant-depleted lung injury. Crit Care Med 30:422-7
Chang, Hung; Lai-Fook, Stephen J; Domino, Karen B et al. (2002) Spatial distribution of ventilation and perfusion in anesthetized dogs in lateral postures. J Appl Physiol 92:745-62
Kreck, T C; Shade, E D; Lamm, W J et al. (2001) Isocapnic hyperventilation increases carbon monoxide elimination and oxygen delivery. Am J Respir Crit Care Med 163:458-62
Kreck, T C; Krueger, M A; Altemeier, W A et al. (2001) Determination of regional ventilation and perfusion in the lung using xenon and computed tomography. J Appl Physiol 91:1741-9
Lim, C M; Domino, K B; Glenny, R W et al. (2001) Effect of increasing perfluorocarbon dose on VA/Q distribution during partial liquid ventilation in acute lung injury. Anesthesiology 94:637-42
Hubler, M; Souders, J E; Shade, E D et al. (2001) Effects of vaporized perfluorocarbon on pulmonary blood flow and ventilation/perfusion distribution in a model of acute respiratory distress syndrome. Anesthesiology 95:1414-21
Brogan, T V; Hedges, R G; McKinney, S et al. (2000) Pulmonary NO synthase inhibition and inspired CO2: effects on V'/Q' and pulmonary blood flow distribution. Eur Respir J 16:288-95

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